Estrogen has an important role in stimulating the growth of
breast carcinomas. Inhibition of
estrogen production is therefore a logical treatment strategy. A number of selective inhibitors have been developed against
aromatase, a
cytochrome P-450 enzyme which catalyzes the rate limiting step in the biosynthesis of
estrogens. The mechanisms of the
aromatase reaction, current knowledge of the
enzyme, and regulation of its expression are discussed as the basis for inhibitor development. Two classes of
aromatase inhibitors, steroidal and non-steroidal compounds, are now coming into use. Among the
steroid substrate analogues,
4-hydroxyandrostenedione (4-OHA) has been shown to be effective in
breast cancer patients with advanced disease and was recently approved for treatment in the United Kingdom. Several different classes of compounds which act as
aromatase inhibitors are currently in clinical trials and should provide
breast cancer patients with a number of treatment options. Among these are highly potent and selective non-steroidal inhibitors which have recently been found to suppress plasma and urinary
estrogens over 95% in
breast cancer patients. The potency of these newer
aromatase inhibitors provides the opportunity to determine whether complete suppression of
estrogen production and action will result in enhanced
tumor regression.